Reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other country.
Bibliographic details of the publications referred to by author in this specification are collected at the end of the description.
Proteins have been traditionally regarded as linear chains of amino acids which fold into a defined three-dimensional shape necessary to enable their biological function. In many proteins, the linear peptide backbone is cross-linked via disulfide bonds between cysteine residues but even in these cases, the three dimensional folds are generally topologically simple and are not knotted.
Certain plants of the Rubiaceae and Violaceae families provide small cyclic proteins in the order of approximately 30 amino acids. The cyclization involves an amide bond resulting in no identifiable N- or C-terminus in the molecule. Notable examples of these small cyclic molecules are the circulins (Gustafson et al, 1994), kalata B1 (Saether et al, 1995), cyclopsychotride (Witherup et al, 1994) and several molecules from the Violaceae family (Schopke et al, 1993; Claeson et al, 1998; Goransson et al, 1999).
These small cyclic proteins have diverse activities including anti-microbial properties, haemolytic activities and as uterotonic agents. However, the biological function of cyclic proteins in plants is largely unknown.
In work leading up to the present invention, the inventors have characterized a new family of cyclic proteins. The cyclic proteins exhibit conserved cysteine residues defining a structure referred to herein as a “cystine knot”. This family includes both naturally occurring cyclic molecules and their linear derivatives as well as linear molecules which have undergone cyclization. These molecules are useful as molecular framework structures having enhanced stability over their linear counterparts.